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Metabolic Acidosis Cirrhosis

Review. Perioperative Management Of Lactic Acidosis In End-stage Liver Disease Patient

Review. Perioperative Management Of Lactic Acidosis In End-stage Liver Disease Patient

1. Kreisberg RA. Lactate Homeostasis and Lactic Acidosis, Ann. of Int. Med. 1980;92: 227-237. 2. Gunnerson KJ1, Saul M, He S, Kellum JA. Lactate versus nonlactate metabolic acidosis: a retrospective outcome evaluation of critically ill patients Crit Care 2006; 10:R22. 3. Cohen RD, Woods HF. Clinical and biochemical aspects of lactic acidosis. Blackwell Scientific Publication, Oxford, 1976 pp.46-64. 4. Kraut J., Madias N. Lactic Acidosis N Engl J Med. 2014 Dec 11;371:2309-19. 5. Jeppesen JB, Mortensen C, Bendtsen F, Mller S. Lactate metabolism in chronic liver disease. Scand J Clin Lab Invest Scand J Clin Lab Invest. 2013;73:293-9. 6. Bakker J, Nijsten MW, Jansen TC. Clinical use of lactate monitoring in critically ill patients. Ann Intensive Care. 2013 May 10;3:12. 7. Murphy ND, Kodakat SK, Wendon JA, et al. Liver and intestinal lactate metabolism in patients with acute hepatic failure undergoing liver transplantation. Crit Care Med 2001; 29: 2111-8. 8. Oster JR, Perez GO. Acid-base disturbances in liver disease. J Hepatol 1986; 2: 299-306. 9. Walsh TS, Mclellan S, Mackenzie SJ, et al. Hyperlactatemia and pulmonary lactate production in patients with fulminant hepatic failure. Chest 1999; 116: 471-6. 10. Bernardi M, Predieri S. Disturbances of acid-base balance in cirrhosis: a neglected issue warranting further insights. Liver Int 2005;25:463-6. 11. Funk G., Doberer D., Kneidinger N., et al. Acid-base disturbances in critically ill patients with cirrhosis. Liver International 2007 ISSN 1478-3223 p.901-909. 12. Fencl V, Leith D. Stewarts quantitative acid-base chemistry: Applications in biology and medicine Resp. Physiol. 1993;91: 1-16. 13. Fencl V, Jabor A, Kazda A, Figge J. Diagnosis of metabolic acidbase disturbances in critically ill patients. Am J Respir Crit Care Continue reading >>

Alterations In Arterial Blood Parameters In Patients With Liver Cirrhosis And Ascites

Alterations In Arterial Blood Parameters In Patients With Liver Cirrhosis And Ascites

Int J Med Sci 2007; 4(2):94-97. doi:10.7150/ijms.4.94 Alterations in Arterial Blood Parameters in Patients with Liver Cirrhosis and Ascites Konstantinos Charalabopoulos1,2, Dimitrios Peschos3, Leonidas Zoganas4, George Bablekos4, Christos Golias1, Alexander Charalabopoulos1, Dimitrios Stagikas1, Angi Karakosta1, Athanasios Papathanasopoulos5, George Karachalios2, Anna Batistatou3 1. Department of Physiology, Clinical Unit, Medical Faculty, University of Ioannina, Ioannina, Greece. 2. Department of Medicine, Red Cross Hospital, Athens, Greece. 3. Department of Pathology, Medical Faculty, University of Ioannina, Ioannina, Greece. 4. Department of Thoracic Surgery, Red Cross Hospital, Athens, Greece. 5. Department of Medicine, Gastroenterology Unit, Medical Faculty, University of Ioannina, Ioannina, Greece. This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) License . See for full terms and conditions. Charalabopoulos K, Peschos D, Zoganas L, Bablekos G, Golias C, Charalabopoulos A, Stagikas D, Karakosta A, Papathanasopoulos A, Karachalios G, Batistatou A. Alterations in Arterial Blood Parameters in Patients with Liver Cirrhosis and Ascites. Int J Med Sci 2007; 4(2):94-97. doi:10.7150/ijms.4.94. Available from In cirrhotic patients, in addition to hepatocytes and Kuppfer cells dysfunction circulatory anatomic shunt and ventilation/perfusion (VA/ Q) ratio abnormalities can induce decrease in partial pressure of oxygen in arterial blood (PaO2), in oxygen saturation of hemoglobin (SaO2) as well as various acid-base disturbances. We studied 49 cases of liver cirrhosis (LC) with ascites compared to 50 normal controls. Causes were: posthepatic 37 (75.51%), alcoholic 7 (14.24%), cardiac 2 (4.08%), and cryptogenic 3 (6.12%). C Continue reading >>

Renal Tubular Acidosis: The Clinical Entity

Renal Tubular Acidosis: The Clinical Entity

Renal Tubular Acidosis: The Clinical Entity Department of Pediatrics, Hospital de Cruces, Vizcaya, Spain. Correspondence to Professor J. Rodrguez-Soriano, Department of Pediatrics, Hospital de Cruces, Plaza de Cruces s/n, Baracaldo, 48903 Vizcaya, Spain. Phone: 34-94-6006357; Fax: 34-94-6006044; E-mail: jsoriano{at}hcru.osakidetza.net The term renal tubular acidosis (RTA) is applied to a group of transport defects in the reabsorption of bicarbonate (HCO3), the excretion of hydrogen ion (H+), or both. This condition was first described in 1935 ( 1 ), confirmed as a renal tubular disorder in 1946 ( 2 ), and designated renal tubular acidosis in 1951 ( 3 ). The RTA syndromes are characterized by a relatively normal GFR and a metabolic acidosis accompanied by hyperchloremia and a normal plasma anion gap. In contrast, the term uremic acidosis is applied to patients with low GFR in whom metabolic acidosis is accompanied by normo- or hypochloremia and an increased plasma anion gap. The renal acid-base homeostasis may be broadly divided into two processes: (1) reabsorption of filtered HCO3, which occurs fundamentally in the proximal convoluted tubule; and (2) excretion of fixed acids through the titration of urinary buffers and the excretion of ammonium, which takes place primarily in the distal nephron. The mechanisms for proximal reabsorption of approximately 80 to 90% of filtered HCO3 are displayed in Figure 1 . The foremost processes occurring in this segment are H+ secretion at the luminal membrane via a specific Na+- H+ exchanger (NHE-3) and HCO3 transport at the basolateral membrane via a Na+- HCO3 cotransporter (NBC-1). In the proximal tubules, carbonic acid (H2CO3) is formed within the cell by the hydration of CO2, a reaction catalyzed by a soluble cytoplasmic carbonic Continue reading >>

Metabolic Acidosis-normal Anion Gap (non-anion Gap Metabolic Acidosis, Nagma)

Metabolic Acidosis-normal Anion Gap (non-anion Gap Metabolic Acidosis, Nagma)

MD Nexus > Renal > Metabolic Acidosis-Normal Anion Gap (Non-Anion Gap Metabolic Acidosis, NAGMA) Metabolic Acidosis-Normal Anion Gap (Non-Anion Gap Metabolic Acidosis, NAGMA) Type 1 Distal RTA (see Type 1 Distal Renal Tubular Acidosis ) Ehlers-Danlos Syndrome (see Ehlers-Danlos Syndrome ) Familial Type 1 Distal Renal Tubular Acidosis Medullary Cystic Disease: produces both distal RTA and proximal RTA Renal Transplant Rejection (see Renal Transplant ) Milk Alkali Syndrome (see Milk Alkali Syndrome ) Primary Hyperoxaluria (see Primary Primary Hyperoxaluria ) Primary/Familial Hyperparathyroidism (see Hyperparathyroidism ) Rheumatoid Arthritis (RA) (see Rheumatoid Arthritis ) Sjogrens Syndrome (see Sjogrens Syndrome ): produces both distal RTA and proximal RTA Multiple Myeloma (see Multiple Myeloma ): produces both distal RTA and proximal RTA Non-Steroidal Anti-Inflammatory Drugs (NSAID) (see Non-Steroidal Anti-Inflammatory Drug ) Ifosfamide (see Ifosfamide ): produces both distal RTA and proximal RTA Human Immunodeficiency Virus (HIV)/AIDS (see Human Immunodeficiency Virus ): possible etiology Idiopathic (Sporadic) Type 1 Distal Renal Tubular Acidosis Type 2 Proximal RTA (see Type 2 Proximal Renal Tubular Acidosis ) Proximal Tubule Cell Sodium Bicarbonate Co-Transporter (NBCe1) Defect Wilson Disease (see Wilson Disease , [[Wilson Disease]]): produces both distal and proximal RTA Sjogrens Syndrome (see Sjogrens Syndrome ) Acetazolamide (Diamox) (see Acetazolamide , [[Acetazolamide]]) Physiology: carbonic anhydrase inhibition -> bicarbonate loss in urine Carbonic Anhydrase II Deficiency/Osteopetrosis Dichlorphenamide (Keveyis) (see Dichlorphenamide , [[Dichlorphenamide]]) Physiology: carbonic anhydrase inhibition -> bicarbonate loss in urine Mafenide Acetate (Sulfamylon) (s Continue reading >>

American Thoracic Society - Liver Dysfunction And Severe Lactic Acidosis In A Previously Healthy Man

American Thoracic Society - Liver Dysfunction And Severe Lactic Acidosis In A Previously Healthy Man

Liver dysfunction and severe lactic acidosis in a previously healthy man A man in his eighth decade presented to his primary doctor three weeks prior to admission with easy bruising. A complete blood count revealed low counts in all three major cell lines and a subsequent bone marrow biopsy demonstrated B-cell follicular lymphoma. Other biochemical parameters, including tests of liver transaminases and bilirubin, were normal. Two weeks later he developed a cough and shortness of breath and he received a diagnosis of acute bronchitis, for which he was prescribed azithromycin along with an inhaler of salmeterol and fluticasone. His cough and dyspnea did not improve and he was admitted to another hospital for further evaluation. A diagnosis of liver failure was made based on elevated liver function tests (aspartate aminotransferase=995 U/L, alanine aminotransferase=552 U/L, total bilirubin=7.2 mg/dL, direct bilirubin=5.5 mg/dL); worsening pancytopenia was noted. Evaluation of the acute liver failure did not reveal an etiology, and he was transferred to a tertiary care hospital for further evaluation and care. Thyroid cancer, s/p partial thyroidectomy Denies excessive alcohol and illicit drug use 40 pack-year cigarette smoking history, stopped in 2004 Laboratory investigation did not reveal occult infectious hepatitis or autoimmune disease. Diagnostic imaging of the liver revealed a large intra-hepatic mass and trans-jugular liver biopsy showed extensive hepatic infiltration by lymphoma. His respiratory status became increasingly tenuous and his trachea was intubated and positive-pressure mechanical ventilation was initiated. He was transferred to the ICU but suffered the rapid onset of shock despite infusions of sodium bicarbonate and norepinephrine. After a conversation Continue reading >>

Acid-base And Potassium Disorders In Liver Disease

Acid-base And Potassium Disorders In Liver Disease

Northwestern University, Feinberg school of Medicine, Chicago Acid-base and potassium disorders occur frequently in the setting of liver disease. As the liver's metabolic function worsens, particularly in the setting of renal dysfunction, hemodynamic compromise, and hepatic encephalopathy, acid-base disorders ensue. The most common acid-base disorder is respiratory alkalosis. Metabolic acidosis alone or in combination with respiratory alkalosis also is common. Acid-base disorders in patients with liver disease are complex. The urine anion gap may help to distinguish between chronic respiratory alkalosis and hyperchloremic metabolic acidosis when a blood gas is not available. A negative urine anion gap helps to rule out chronic respiratory alkalosis. In this disorder a positive urine anion gap is expected owing to suppressed urinary acidification. Distal renal tubular acidosis occurs in autoimmune liver disease such as primary biliary cirrhosis, but often is a functional defect from impaired distal sodium delivery. Potassium disorders are often the result of the therapies used to treat advanced liver disease. Do you want to read the rest of this article? ... Patients with decompensated liver disease, in the setting of sepsis or hemorrhage, may have increased serum lactate levels due to poor utilization and metabolism. [29] Lactic acidosis may be precipitated by biguanides as they inhibit mitochondrial respiration predominantly in the liver. ... Continue reading >>

Hepatic Encephalopathy In Patients With Acute Decompensation Of Cirrhosis And Acute-on-chronic Liver Failure - Sciencedirect

Hepatic Encephalopathy In Patients With Acute Decompensation Of Cirrhosis And Acute-on-chronic Liver Failure - Sciencedirect

Hepatic encephalopathy in patients with acute decompensation of cirrhosis and acute-on-chronic liver failure Author links open overlay panel ManuelRomero-Gmez1 Hepatic encephalopathy in a hospitalized cirrhotic patient is associated with a high mortality rate and its presence adds further to the mortality of patients with acute-on-chronic liver failure (ACLF). The exact pathophysiological mechanisms of HE in this group of patients are unclear but hyperammonemia, systemic inflammation (including sepsis, bacterial translocation, and insulin resistance) and oxidative stress, modulated by glutaminase gene alteration, remain as key factors. Moreover, alcohol misuse, hyponatremia, renal insufficiency, and microbiota are actively explored. HE diagnosis requires exclusion of other causes of neurological, metabolic and psychiatric dysfunction. Hospitalization in the ICU should be considered in every patient with overt HE, but particularly if this is associated with ACLF. Precipitating factors should be identified and treated as required. Evidence-based specific management options are limited to bowel cleansing and non-absorbable antibiotics. Ammonia lowering drugs, such as glycerol phenylbutyrate and ornithine phenylacetate show promise but are still in clinical trials. Albumin dialysis may be useful in refractory cases. Antibiotics, prebiotics, and treatment of diabetes reduce systemic inflammation. Where possible and not contraindicated, large portal-systemic shunts may be embolized but liver transplantation is the most definitive step in the management of HE in this setting. HE in patients with ACLF appears to be clinically and pathophysiologically distinct from that of acute decompensation and requires further studies and characterization. Continue reading >>

Hepatic Encephalopathy

Hepatic Encephalopathy

Hepatic encephalopathy (HE) describes a spectrum of potentially reversible neuropsychiatric abnormalities seen in patients with liver dysfunction after exclusion of unrelated neurologic and/or metabolic abnormalities. The term implies that altered brain function is due to metabolic abnormalities. The full reversibility of symptoms after improvement of liver function is considered to be direct proof of this causal relation. An important prerequisite for the syndrome is diversion of portal blood into the systemic circulation through portosystemic collateral vessels. 1 Expression of encephalopathy is characterized by personality changes, intellectual impairment, and may advance to a depressed level of consciousness. In patients with cirrhosis, acute encephalopathy is most commonly associated with a precipitating factor, such as electrolyte disturbance, medications, gastrointestinal hemorrhage, or infection. 2 Those with fulminant hepatic failure may experience altered mental status, severe cerebral edema and subsequent herniation of brain stem with fatal consequences. Detailed discussion of this entity is beyond the scope of this chapter. HE may be clinically apparent in as many as one third of cirrhotic patients and, if rigorously tested, up to two thirds have some degree of mild or subclinical HE. While the precise molecular mechanisms that result in these morphological changes in the brain are yet to be identified, many factors have been elucidated, especially the role of ammonia, false neurotransmitters, astrocyte swelling, inflammation, and oxidative stress. Ammonia, a byproduct of the metabolism of nitrogen-containing compounds, is neurotoxic at elevated concentrations. 3 The liver clears almost all of the portal vein ammonia, converting it into glutamine and urea p Continue reading >>

Acid-base And Potassium Disorders In Liver Disease.

Acid-base And Potassium Disorders In Liver Disease.

Acid-base and potassium disorders in liver disease. Division of Nephrology and Hypertension, Department of Medicine, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. [email protected] Acid-base and potassium disorders occur frequently in the setting of liver disease. As the liver's metabolic function worsens, particularly in the setting of renal dysfunction, hemodynamic compromise, and hepatic encephalopathy, acid-base disorders ensue. The most common acid-base disorder is respiratory alkalosis. Metabolic acidosis alone or in combination with respiratory alkalosis also is common. Acid-base disorders in patients with liver disease are complex. The urine anion gap may help to distinguish between chronic respiratory alkalosis and hyperchloremic metabolic acidosis when a blood gas is not available. A negative urine anion gap helps to rule out chronic respiratory alkalosis. In this disorder a positive urine anion gap is expected owing to suppressed urinary acidification. Distal renal tubular acidosis occurs in autoimmune liver disease such as primary biliary cirrhosis, but often is a functional defect from impaired distal sodium delivery. Potassium disorders are often the result of the therapies used to treat advanced liver disease. Continue reading >>

Cirrhosis

Cirrhosis

Cirrhosis is severe scarring of the liver caused by chronic liver disease . As healthy liver tissue is damaged over a long period of time, it is replaced by scar tissue, affecting the structure of the liver and decreasing its ability to function. It is linked to approximately 32,000 deaths annually in the United States. Cirrhosis is seen with a variety of chronic liver diseases and may take years or even decades to develop. Unlike scars in other parts of the body, some of the scarring that occurs in the liver is reversible, even in people with cirrhosis. The liver is a vital organ located in the upper right-hand side of the abdomen. Among other functions, it helps convert nutrients from food into essential blood components, produces many of the factors necessary for normal blood clotting, metabolizes and detoxifies substances that would otherwise be harmful to the body, and produces bile a fluid necessary for the digestion of fats. Liver diseases can affect any of these functions. These diseases may be the result of infection, physical injury, exposure to a toxin , an autoimmune process, or due to a genetic defect that leads to the build-up of substances such as copper or iron. The damage that liver diseases cause can lead to inflammation, obstruction to bile flow, and clotting abnormalities. Prolonged and persistent damage can lead to the accumulation of excess connective tissue, or fibrosis of the liver, which is how cirrhosis develops. With cirrhosis, the structure of the liver changes, forming nodules of cells surrounded by fibrous tissue. This tissue does not function like healthy liver tissue and can interfere with the flow of blood and bile through the liver. As cirrhosis progresses, it can begin to affect other organs and tissues throughout the body. Some examp Continue reading >>

Causes Of Lactic Acidosis

Causes Of Lactic Acidosis

INTRODUCTION AND DEFINITION Lactate levels greater than 2 mmol/L represent hyperlactatemia, whereas lactic acidosis is generally defined as a serum lactate concentration above 4 mmol/L. Lactic acidosis is the most common cause of metabolic acidosis in hospitalized patients. Although the acidosis is usually associated with an elevated anion gap, moderately increased lactate levels can be observed with a normal anion gap (especially if hypoalbuminemia exists and the anion gap is not appropriately corrected). When lactic acidosis exists as an isolated acid-base disturbance, the arterial pH is reduced. However, other coexisting disorders can raise the pH into the normal range or even generate an elevated pH. (See "Approach to the adult with metabolic acidosis", section on 'Assessment of the serum anion gap' and "Simple and mixed acid-base disorders".) Lactic acidosis occurs when lactic acid production exceeds lactic acid clearance. The increase in lactate production is usually caused by impaired tissue oxygenation, either from decreased oxygen delivery or a defect in mitochondrial oxygen utilization. (See "Approach to the adult with metabolic acidosis".) The pathophysiology and causes of lactic acidosis will be reviewed here. The possible role of bicarbonate therapy in such patients is discussed separately. (See "Bicarbonate therapy in lactic acidosis".) PATHOPHYSIOLOGY A review of the biochemistry of lactate generation and metabolism is important in understanding the pathogenesis of lactic acidosis [1]. Both overproduction and reduced metabolism of lactate appear to be operative in most patients. Cellular lactate generation is influenced by the "redox state" of the cell. The redox state in the cellular cytoplasm is reflected by the ratio of oxidized and reduced nicotine ad Continue reading >>

Metabolic Acidosis And Alkalosis

Metabolic Acidosis And Alkalosis

Page Index Metabolic Acidosis. Metabolic Alkalosis Emergency Therapy Treating Metabolic Acidosis Calculating the Dose Use Half the Calculated Dose Reasons to Limit the Bicarbonate Dose: Injected into Plasma Volume Fizzes with Acid Causes Respiratory Acidosis Raises Intracellular PCO2 Subsequent Residual Changes Metabolic Acidosis. The following is a brief summary. For additional information visit: E-Medicine (Christie Thomas) or Wikepedia Etiology: There are many causes of primary metabolic acidosis and they are commonly classified by the anion gap: Metabolic Acidosis with a Normal Anion Gap: Longstanding diarrhea (bicarbonate loss) Uretero-sigmoidostomy Pancreatic fistula Renal Tubular Acidosis Intoxication, e.g., ammonium chloride, acetazolamide, bile acid sequestrants Renal failure Metabolic Acidosis with an Elevated Anion Gap: lactic acidosis ketoacidosis chronic renal failure (accumulation of sulfates, phosphates, uric acid) intoxication, e.g., salicylates, ethanol, methanol, formaldehyde, ethylene glycol, paraldehyde, INH, toluene, sulfates, metformin. rhabdomyolysis For further details visit: E-Medicine (Christie Thomas). Treating Severe Metabolic Acidosis. The ideal treatment for metabolic acidosis is correction of the underlying cause. When urgency dictates more rapid correction, treatment is based on clinical considerations, supported by laboratory evidence. The best measure of the level of metabolic acidosis is the Standard Base Excess (SBE) because it is independent of PCO2. If it is decided to administer bicarbonate, the SBE and the size of the treatable space are used to calculate the dose required: Metabolic Alkalosis Etiology: Primary Metabolic alkalosis may occur from various causes including: Loss of acid via the urine, stools, or vomiting Transfer of Continue reading >>

Spontaneous Bacterial Peritonitis And Henoch-schnlein Purpura In A Patient With Liver Cirrhosis

Spontaneous Bacterial Peritonitis And Henoch-schnlein Purpura In A Patient With Liver Cirrhosis

Spontaneous Bacterial Peritonitis and Henoch-Schnlein Purpura in a Patient with Liver Cirrhosis Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USA Received 23 February 2015; Accepted 15 April 2015 Copyright 2015 Neil Gupta et al. This is an open access article distributed under the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Henoch-Schnlein purpura (HSP) is a small vessel systemic vasculitis, predominantly affecting children, characterized by a tetrad of manifestations, specifically palpable purpura, arthralgia, abdominal pain, and renal disease. HSP in the adult population is rare, and no case has been described of HSP in liver cirrhosis with spontaneous bacterial peritonitis (SBP). We present the case of a 58-year-old male with liver cirrhosis, who was subsequently diagnosed with SBP and later HSP. In this patient, the diagnosis of HSP was demonstrated clinically by his palpable purpura, diarrhea, hematuria, and abdominal pain and confirmed pathologically by his renal and skin biopsies demonstrating leukocytoclastic vasculitis and IgA complexes. We believe that this is an example of altered IgA processing in cirrhosis leading to the development of IgA immune complexes and ultimately HSP. The patient additionally had SBP, which may have increased his risk for developing HSP given antigen processing by mucosa-associated lymphoid tissues leading to immune complex deposition, which may not have been effectively cleared in the context of his liver disease. The patient unfortunately died of gastrointestinal hemorrhage, which is unclear to be due to his underlying cirrhosis or a gastrointestinal manifestation of HSP itself. Henoc Continue reading >>

Metabolic Acidosis: Practice Essentials, Background, Etiology

Metabolic Acidosis: Practice Essentials, Background, Etiology

Metabolic acidosis is a clinical disturbance characterized by an increase in plasma acidity. Metabolic acidosis should be considered a sign of an underlying disease process. Identification of this underlying condition is essential to initiate appropriate therapy. (See Etiology, DDx, Workup, and Treatment.) Understanding the regulation of acid-base balance requires appreciation of the fundamental definitions and principles underlying this complex physiologic process. Go to Pediatric Metabolic Acidosis and Emergent Management of Metabolic Acidosis for complete information on those topics. An acid is a substance that can donate hydrogen ions (H+). A base is a substance that can accept H+ ions. The ion exchange occurs regardless of the substance's charge. Strong acids are those that are completely ionized in body fluids, and weak acids are those that are incompletely ionized in body fluids. Hydrochloric acid (HCl) is considered a strong acid because it is present only in a completely ionized form in the body, whereas carbonic acid (H2 CO3) is a weak acid because it is ionized incompletely, and, at equilibrium, all three reactants are present in body fluids. See the reactions below. The law of mass action states that the velocity of a reaction is proportional to the product of the reactant concentrations. On the basis of this law, the addition of H+ or bicarbonate (HCO3-) drives the reaction shown below to the left. In body fluids, the concentration of hydrogen ions ([H+]) is maintained within very narrow limits, with the normal physiologic concentration being 40 nEq/L. The concentration of HCO3- (24 mEq/L) is 600,000 times that of [H+]. The tight regulation of [H+] at this low concentration is crucial for normal cellular activities because H+ at higher concentrations can b Continue reading >>

8.1 Lactic Acidosis

8.1 Lactic Acidosis

Lactic acidosis is a common cause of metabolic acidosis. 1,2,3 Each day the body has an excess production of about 1500 mmols of lactate (about 20 mmols/kg/day) which enters the blood stream and is subsequently metabolised mostly in the liver. This internal cycling with production by the tissues and transport to and metabolism by the liver and kidney is known as the Cori cycle. This normal process does not represent any net fixed acid production which requires excretion from the body. All tissues can produce lactate under anaerobic conditions but tissues with active glycolysis produce excess lactate from glucose under normal conditions and this lactate tends to spill over into the blood. Lactate is produced from pyruvate in a reaction catalysed by lactate dehydrogenase: This reaction is so rapid that pyruvate and lactate can be considered to be always in an equilibrium situation. Normally the ratio of lactate to pyruvate in the cell is 10 to 1. The ratio [NADH]/[NAD+] by the Law of Mass Action determines the balance between lactate and pyruvate. This ratio is also used to denote the redox state within the cytoplasm. Lactic acid has a pK value of about 4 so it is fully dissociated into lactate and H+ at body pH. In the extracellular fluid, the H+ titrates bicarbonate on a one for one basis. Lactate is released from cells into the ISF and blood. At rest, the tissues which normally produce excess lactate are: During heavy exercise, the skeletal muscles contribute most of the much increased circulating lactate.( 4,5 ) During pregnancy, the placenta is an important producer of lactate which passes into both the maternal and the foetal circulations. Lactate is metabolised predominantly in the liver (60%) and kidney (30%) 6 . Half is converted to glucose (gluconeogenesis) and Continue reading >>

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